Sea lice are parasitic crustaceans/copepods within the order Siphonostomatoida, family Caligidae that feed on the mucus, epidermal tissue, and blood of host marine fish. Johnson et al, Parasitol Res (2002) 88: 789-796. Sea lice are prevalent parasites, particularly on salmonids, and, when present in high numbers, can cause serious disease and ultimately host death. In fish farms, where highly concentrated fish populations are present, sea lice can have a devastating effect on the stock.
In 2006, total salmonid marine production was 1.7 million tons, worth US $8.4 billion. See FAO Fisheries and Aquaculture Information and Statistics Service 2008, Aquaculture Production 1950-2006. Available data indicates sea lice cost from 0.1 to 0.2 kg−1 of fish. Mark J Costello, The global economic cost of sea lice to the salmonid farming industry, Journal of Fish Diseases, v. 32(1), pgs 115-118 (2009). However, without treatment measures, sea lice would cost the industry at least four times more and probably increase to levels such as to cause significant direct and indirect mortality, to stock. Mustafa et al, Canadian Veterinary Journal 42, 54-56 (2001). Existing regional estimates for the cost of sea lice ranged from 4% of production value for Atlantic Canada to 7-10% in Scotland. Rae et al, Pest Management Science 58, 515-520 (2002)). Notably, Costello et al., supra, indicates a cost of 6% of the value of fish production for the countries affected by sea lice.
To date, available treatment regimens against sea lice infestations have been very limited, i.e., SLICE® (macrocyclic lactone—emamectin benzoate; U.S. Pat. No. 6,486,128 B1), being the only significant oral commercial treatment available. Additional ectoparasiticidal compounds have been explored, such as those described in U.S. Pat. No. 8,128,943 B2 and U.S. Pat. No. 6,538,031 B1, but no successful treatment agents based on these disclosures have emerged. Additionally, studies have been conducted on vaccine compositions targeting antigens present in sea lice, but no products using the vaccine approach have emerged either.
Accordingly, SLICE® has been widely used and as a result, significant resistance amongst sea lice populations has arisen, thought to be associated with its macrocyclic lactone structure, which occurs in other parasitic disease states targeted by macrocyclic lactones.
Accordingly, a need exists for a novel agent capable of treating sea lice infestations in fish, particularly in farmed fish populations, that is safe and selective against the target parasite and is capable of treating sea lice populations showing emamectin resistance.
Selamectin is a macrocyclic lactone used as a topical parasiticide and antihelminthic for dogs and cats. The antiparasitic activity of selamectin, a compound belonging to the class of avermectins, was disclosed in International Patent Application WO1994/15944 (Example 5) and is currently marketed as a topical pour-on for companion animal (dogs and cats) use under the trade name, Revolution®.
Like selamectin, emamectin also is an avermectin derivative and a macrocyclic lactone. Thus, one would expect sea lice resistance observed for emamectin to co-exist with selamectin. The invention surprisingly demonstrated that selamectin overcomes many of the disadvantages and resistance mechanisms associated with emamectin/SLICE®, in part due to its potency.